Vascular reactivity to angiotensin II in human pregnancy

The results obtained in this study are consistent with the concept that during normal human pregnancy prostaglandin(s) or prostaglandin-related substance(s) are involved in the mediation or control of vascular reactivity to angiotensin II, since the administration of prostaglandin synthetase inhibitors is associated with a significant alteration in vascular reactivity to angiotensin II. Specifically, indomethacin and aspirin treatment of normal pregnant women is associated with a significant reduction in the amount of infused angiotensin II required to evoke a rise of 20 mm Hg in diastolic blood pressure. Thus it appears that the refractoriness to angiotensin II usually observed during normal pregnancy may be mediated by the action of prostaglandins or related substances produced in situ in the arterioles. Decreases in the rate of prostaglandin synthesis or increases in the rate of prostaglandin catabolism could result in increased vascular responsiveness to infused angiotensin II, a characteristic of the pregnant woman who has developed or is destined to develop pregnancy-induced hypertension. Based on these observations, it also is apparent that potential hazards may obtain in the gravida who ingests agents known to inhibit the prostaglandin synthetase complex. The use of prostaglandin synthetase inhibitors, e.g., indomethacin or aspirin, in attempts to prevent or arrest premature labor could prove hazardous to the fetus, not only through premature closure of the fetal ductus arteriosus but also through an increase in maternal vascular response to pressor agents. Certainly an increase in vascular responsiveness to angiotensin II could result in significant maternal vasoconstriction. This may be even a greater hazard if these agents are administered to gravidas already sensitive to angiotensin II, such as those who are destined to develop pregnancy-induced hypertension. It should also be noted that if the angiotensin II infusion test or the rollover test is used as a screening test to identify those women destined to develop pregnancy-induced hypertension, the ingestion of indomethacin or aspirin may result in a false positive test.